Pediatric Patients Demonstrate Progressive T1-Weighted Hyperintensity in the Dentate Nucleus following Multiple Doses of Gadolinium-Based Contrast Agent.

BACKGROUND AND PURPOSE: While there have been recent reports of brain retention of gadolinium following gadolinium-based contrast agent administration in adults, a retrospective series of pediatric patients has not previously been reported, to our knowledge. We investigated the relationship between the number of prior gadolinium-based contrast agent doses and increasing T1 signal in the dentate nucleus on unenhanced T1-weighted MR imaging. We hypothesized that despite differences in pediatric physiology and the smaller gadolinium-based contrast agent doses that pediatric patients are typically administered based on weighted-adjusted dosing, the pediatric brain would also demonstrate dose-dependent increasing T1 signal in the dentate nucleus. MATERIALS AND METHODS: We included children with multiple gadolinium-based contrast agent administrations at our institution. A blinded reader placed ROIs within the dentate nucleus and adjacent cerebellar white matter. To eliminate reader bias, we also performed automated ROI delineation of the dentate nucleus, cerebellar white matter, and pons. Dentate-to-cerebellar white matter and dentate-to pons ratios were compared with the number of gadolinium-based contrast agent administrations. RESULTS: During 20 years at our institution, 280 patients received at least 5 gadolinium-based contrast agent doses, with 1 patient receiving 38 doses. Sixteen patients met the inclusion/exclusion criteria for ROI analysis. Blinded reader dentate-to-cerebellar white matter ratios were significantly associated with gadolinium-based contrast agent doses (rs = 0.77, P = .001). The dentate-to-pons ratio and dentate-to-cerebellar white matter ratios based on automated ROI placement were also significantly correlated with gadolinium-based contrast agent doses (t = 4.98, P < .0001 and t = 2.73, P < .02, respectively). CONCLUSIONS: In pediatric patients, the number of prior gadolinium-based contrast agent doses is significantly correlated with progressive T1-weighted dentate hyperintensity. Definitive confirmation of gadolinium deposition requires tissue analysis. Any potential clinical sequelae of gadolinium retention in the developing brain are unknown. Given this uncertainty, we suggest taking a cautious stance, including the use, in pediatric patients, of higher stability, macrocyclic agents, which in both human and animal studies have been shown to be associated with lower levels of gadolinium deposition, and detailed documentation of dosing. Most important, a patient should not be deprived of a well-indicated contrasted MR examination.

Ultrasound-guided tandem placement for low-dose-rate brachytherapy in advanced cervical cancer minimizes risk of intraoperative uterine perforation.

OBJECTIVES: Tandem placement as part of low-dose-rate (LDR) brachytherapy boost for cervical cancer may be complicated by uterine perforation. The objective of this study was to describe a 10-year experience of using intraoperative ultrasound guidance in an attempt to minimize the risk of uterine perforation. METHODS: Operative and inpatient records were reviewed to identify cases in which intraoperative ultrasound guidance was employed in order to assist tandem placement, and to determine whether clinical or radiographic findings subsequently suggested uterine perforation. Demographic factors were collected in order to determine the baseline risk of perforation within this population. RESULTS: Between 1998 and 2008, 71 patients underwent 110 ultrasound-guided placements of tandem applicators. The median age was 48 (range, 26-88) years, and 20% were older than 60 years. Disease stage was FIGO IB1 (n = 10), IB2 (n = 13), IIA (n = 4), IIB (n = 19), IIIA (n = 2), IIIB (n = 16), IVA (n = 5) and IVB (n = 2). The median gravidity was 3 (range 1-10) and median parity was 3 (range 0-10). Seven patients had a preimplant history of pelvic infection, four had a history of intrauterine contraceptive device use, and 10 had a prior history of Cesarean section delivery. Only one patient experienced infection that may have been attributable to tandem placement-associated uterine perforation. At median survivor follow-up of 34 months, 19 patients had died. The estimated 3-year disease-free and overall survival rates for the entire population were 60% and 66%, respectively. CONCLUSIONS: Within the present population, intraoperative ultrasound guidance of tandem placement was associated with no confirmed cases of uterine perforation.

Fetal dose during radiotherapy: clinical implementation and review of the literature.

Two pregnant patients received radiation therapy, one for the treatment of mediastinal Hodgkin's lymphoma and the other for a head and neck squamous cell carcinoma. The fetuses were both protected by additional shielding which reduced the unshielded exposure of the first fetus by 20-40%, and that of the second by 20-60%. The first child received an estimated maximum dose of 42 cGy, the second a maximum dose of 9 cGy. Treatment details are reported and a review of the literature that addresses the possible irradiation-induced side effects at low doses is included.

Desmoid tumors in a woman with idiopathic multicentric osteolysis: result of three etiologic factors or coincidence?

Desmoid tumors developed on the toes of a young woman with idiopathic multicentric osteolysis (IMO) after amputation of the toenails. A summary of IMO is given, and a review of literature for the etiologic factors of desmoid tumors is added.

Dynamic stereotactic radiosurgery: the Charleston program: a report on the first 150 patients.

We have been pleased with our initial experience in an evolving program. As newer surgical and radiotherapy techniques have become available, the role of radiosurgery has been and will continue to be modified. As more commercially available systems have been marketed, the availability will become more widespread. A battery of residents in neurosurgery and radiation oncology trained in these technologies will provide leadership and future directions of this therapy.

Survival with combined modality therapy after intracerebral recurrence of pleuropulmonary blastoma.

BACKGROUND: We present and discuss the successful treatment of pleuropulmonary blastoma metastatic to the brain using a multimodality regimen with surgery, high-dose chemotherapy and radiation therapy. PROCEDURE: A 3-year-old boy referred to our institution with bilateral pulmonary cysts was diagnosed with pleuropulmonary blastoma (PPB). Initial treatment included surgery and multiagent chemotherapy with vincristine, dactinomycin, cyclophosphamide, cisplatin, and doxorubicin. One year after the completion of therapy, his PPB recurred as an intracerebral metastasis, and required further treatment with a multimodality salvage regimen. The child was successfully treated with a subtotal surgical resection, followed by high-dose cyclophosphamide, and radiation therapy. He is now disease-free 24 months later. RESULTS: Intracerebral metastases of PPB have been a uniformly fatal complication of this tumor. Postsurgical chemotherapy and radiation therapy appear to have contributed to the prolonged survival and potential for cure in our patient. CONCLUSIONS: The use of this multimodality regimen may be warranted in other patients with recurrent PPB metastatic to the brain.

Malignant melanoma: the role of radiation therapy revisited.

In a multidisciplinary approach to the treatment of malignant melanoma, the role of radiation therapy is often relegated to one of minor importance. There is a supporting body of scientific literature that shows a relative radioresistance of melanoma when compared with other malignancies. Others have disputed the notion of resistance and have recommended radiation in a number of clinical settings including not only palliation but also in the primary management of melanoma. This article reviews the current and historical literature to better define the current role of radiation in a multidisciplinary approach for cancer management.

Treatment planning optimization for multiple arcs stereotactic radiosurgery using a linear accelerator.

PURPOSE: Multiarc stereotactic radiosurgery is a technique used to irradiate an intracranial tumor with minimal damage to the surrounding normal tissue. The purpose of this paper is to present a method for and the results from optimizing three dimensional (3D) treatment dose for multiarc stereotactic radiosurgery. METHODS AND MATERIALS: The normal procedure for a physician-physicist team designing a treatment plan for multiarc stereotactic radiosurgery is the trial-and-error approach of changing the collimator size and the isocenter of radiation by viewing the isodose curves on a two dimensional (2D) computed tomography (CT) or magnetic resonance imaging (MRI) image plane. Not only is this time consuming, but the resulting treatment plan is not optimal in most, if not all, cases. One reason for such nonconformal isodose curves is that the same collimator size is used for all arcs. However, it is very difficult to determine manually the different collimator sizes for different arcs. A derivative free optimization method is used to optimize the collimator size for each arc, as well as the 3D coordinates of the isocenter(s). RESULTS: One spherical and two ellipsoidal artificial tumors, and one actual tumor, were used to show the utilities of the optimization process. The 90% isodose curves resulting from optimization conform very well with the tumor; whereas the 90% isodose curves from the conventional method either do not envelop the entire tumor when the collimator size is too small, or a large volume of normal tissue is also irradiated by the 90% dose when the next larger collimator size is used. CONCLUSIONS: When the collimator size for each arc and the location of the isocenters(s) are optimized in a multiarc stereotactic surgery treatment plan, the 90% isodose curve conforms to the tumor much better than when the same collimator size is used for all arcs.

Effect of radiotherapeutic technique on local control in primary vaginal carcinoma.

A retrospective analysis of 73 patients treated for primary vaginal carcinoma with radiation therapy was performed to evaluate the effect of radiotherapeutic technique on local control. Local control was achieved in five of 22 patients (23%) treated with pelvic external beam therapy alone, three of four patients (75%) treated with intracavitary cylinder or Bloedorn applicator alone, and 30 of 47 patients (64%) treated with combination of external beam and brachytherapy. Radiation therapy complications requiring hospitalization occurred in six patients (8%). A statistically significant difference in local control was achieved only when patients receiving external beam and brachytherapy were compared with patients receiving external beam therapy alone (P < 0.005). Total mid-tumor dose was defined as the sum of midplane tumor dose from external beam therapy, mid-tumor dose from interstitial radium needles, and the vaginal surface dose from intracavitary radium systems. Total mid-tumor doses ranged from 16 to 121.7 Gy. Only two of 16 patients receiving less than 55 Gy total mid-tumor dose achieved local control. As a result, dividing doses of 45, 55, 65 and 75 Gy produced a statistically significant superior local control rate in the patients receiving the higher dose (P < 0.01). None of the 16 patients receiving less than 55 Gy total mid-tumor dose had received brachytherapy. We conclude that the combination of external beam therapy and brachytherapy is essential to achieve optimal control of primary vaginal carcinoma.

Combined modality therapy in the treatment of epidermoid carcinoma of the anus at the Medical University of South Carolina.

Treatment of anal epidermoid carcinoma by radiation and chemotherapy does offer an excellent opportunity to maintain quality of life. No patient in this series suffered long-term complications; and all have maintained rectal, anal, and sexual function. Patients with early stage lesions (AJC I-II) are most amenable to anus conserving therapy for epidermoid cancer of the anus. The success rate is markedly diminished in patients having more advanced disease, with patients possessing AJC stage III and VI disease presenting major problems. The possibility of post operative radiation therapy is markedly compromised by preoperative radiation therapy. Clinical surveillance and early recognition of these lesions by primary physicians can now offer patients with lesser stage cancer of this type excellent opportunity for organ preservation therapy. For those patients presenting with Stage III and VI carcinoma of the anus the aforementioned problems should be addressed and discussed before initiating conservative therapy.

Dynamic stereotactic radiosurgery using a linear accelerator.

We describe a system for stereotactic radiosurgery with a linear accelerator. This technique allows treatment of small (less than 40 mm diameter) intracranial lesions, including vascular malformations, and primary and metastatic tumors that are deep within the brain or in areas not amenable to open surgery. A beam of ionizing radiation (1800 to 2500 cGy) is focused on the center of the lesion, which is determined by stereotactic localization. "Dynamic rotation" of the linac gantry and table continuously about this predetermined point ensures that only the lesion receives the full radiation dose, while the normal structures in the head receive minimal amounts of radiation. The system combines, for the first time in one place, elements of radiosurgical technique developed at various centers. Testing for accuracy compares favorably with results at other centers using linac-based systems as well as comparing favorably with the gamma knife.

Primary malignant extragonadal germ cell tumors. An analysis of the effect of the effect of radiotherapy.

A retrospective analysis was performed on all patients diagnosed with biopsy-proven extragonadal germ cell tumors at the University of Virginia (Charlottesville, VA), The Medical University of South Carolina (Charleston, SC), the Bethesda Naval Hospital (Bethesda, MD), and The Medical College of Virginia (Richmond, VA) for the time period of January 1965 to December 1984. A total of 54 patients were treated with the initial sites of presentation observed: mediastinum, 26; central nervous system, 14; retroperitoneum, eight; and sacrococcygeal region, six. Megavoltage irradiation was used in 44 patients with a dose range of 2400 to 5580 cGy (mean, 4213 cGy). With a minimum follow-up of 4.0 years and a mean follow-up of 10.8 years, the 5-year actuarial survival for the entire population was 57.8%. Local control was achieved in 26 of 44 (59%) of the irradiated population. Factors of prognostic significance included histologic type at presentation, site of presentation, and radiation doses greater than or equal to 4000 cGy. Radiotherapy appears to be an effective modality in patients with extragonadal seminomas; however, the nonseminomatous tumors do not appear to be as radioresponsive.

Intraperitoneal P-32 after negative second-look laparotomy in ovarian carcinoma.

Thirty-one patients underwent a negative second-look laparotomy between 1976 and 1986. Fourteen patients received intraperitoneal chromic phosphate (P-32) after a negative second-look laparotomy. There has been no local recurrence (zero of 14) and no deaths attributable to recurrent disease. Local control and disease-free survival are 100%, with a minimum follow-up of 2 years and a mean follow-up of 4 years. Seventeen patients received no further therapy because of patient refusal, poor diffusion, or other contraindications to P-32 installation. Four of 17 patients undergoing negative second-look procedures without the addition of P-32 have subsequently recurred. This difference is highly suggestive (P = .076). There have been no major complications with the addition of P-32. The use of intraperitoneal P-32 after negative second-look laparotomies on ovarian carcinoma is well tolerated and effective in preventing recurrence.

Primary central nervous system germ cell tumors. Effect of histologic confirmation on radiotherapy.

Primary malignant intracranial germ cell tumors are rare lesions responsible for only 0.5% of all central nervous system (CNS) malignancy. With stereotactic localization these lesions can be safely biopsied, and histologic confirmation will affect the ultimate prognosis. This report is a multi-institutional retrospective analysis of 33 patients diagnosed with a primary CNS germ cell tumor. Tumors in 14 patients (42%) were histologically confirmed (13 germinoma and one embryonal cell carcinoma); 19 patients were treated with a presumptive diagnosis. All patients were irradiated with a dose range of 3950 cGy to 6000 cGy to the primary lesions. Eight patients received craniospinal irradiation, and 25 patients were locally treated. The 5-year actuarial survival for the entire population was 64%. The survival rate in patients with histologic confirmation was 79% versus 53% in the unbiopsied population. Radiation doses greater than 5000 cGy, radiotherapy volume, and age were prognostic factors in determining survival.

Radiation enteritis.

As the population receiving radiation therapy grows, so does the incidence of chronic radiation enteritis. A review of the pathology of chronic radiation enteritis reveals fibrosis, endarteritis, edema, fragility, perforation, and partial obstruction. Conservative management of patients with this disease is common. Because the obstruction is only partial, decompression is easily achieved with nasogastric suction and parenteral support. The patient is then often discharged on a liquid-to-soft diet. This therapeutic strategy does nothing for the underlying pathology. The problem, sooner or later, will return with the patient further depleted by the chronic radiation enteritis. We think surgical intervention is appropriate when the diagnosis of chronic radiation enteritis is assumed. The surgery in relation to this disease is high risk with a 30% mortality and 100% expensive morbidity. Early intervention seems to decrease these figures. All anastomoses, if possible, should be outside the irradiated area. Trapped pelvic loops of intestine should be left in place and a bypass procedure with decompressing enterostomies accomplished. The surgery should be performed by a surgeon with extensive experience with all kinds of bowel obstruction as well as experience in performing surgery in radiated tissue.

Primary malignant mediastinal germ-cell tumors and the contribution of radiotherapy: a southeastern multi-institutional study.

A retrospective review was performed by a multi-institutional study group to determine the contribution of radiotherapy to the management of primary malignant mediastinal germ-cell tumors. Twenty-seven patients diagnosed with a primary mediastinal germ-cell tumor between January 1965 and July 1985 form the basis of this study. Twenty-five of the 27 patients were male. Thirteen patients' tumors were diagnosed as seminoma and the remaining 14 patients' tumors had other germ-cell histologies. The single most important prognostic factor was histology, with a 5-year actuarial survival of 100% for the seminomas and only 8.8% for the remaining germ-cell varieties. If total surgical extirpation is not possible, biopsy may be adequate. Of the patients with seminoma, 11 of 12 had local control, and 3 of the 12 patients were treated with doses between 3,000 and 3,100 cGy. High doses for this variety of mediastinal germ-cell tumor might not be required. For the germ-cell tumors other than seminoma, no patient had local control with doses over the range of 3,000-4,750 cGy.

Computed tomography of acute radiation nephritis.

A patient with Hodgkin's disease received a fractionated 3,740 rad dosage over 4 weeks to a portal that included both kidneys. Three months later a computed tomographic scan obtained 2 hours after intravenous contrast injection demonstrated sharply demarcated, dense, persistent nephrograms corresponding to the irradiated areas. These changes are ascribed to acute radiation nephritis, reflecting tubular stasis and ischemia.